You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameAzatadine
Accession NumberDB00719  (APRD00810)
Typesmall molecule
Groupsapproved
Description

Antihistamines such as azatadine appear to compete with histamine for histamine H1- receptor sites on effector cells. The antihistamines antagonize those pharmacological effects of histamine which are mediated through activation of H1- receptor sites and thereby reduce the intensity of allergic reactions and tissue injury response involving histamine release.

Structure
Thumb
Synonyms
SynonymLanguageCode
11-(1-Methyl-4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridineNot AvailableNot Available
6,11-Dihydro-11-(1-methyl-4-piperidylidene)-5H-benzo(5,6)cyclohepta(1,2-b)pyridineNot AvailableNot Available
AzatadinGermanINN
AzatadinaSpanishINN
AzatadineFrenchINN
Azatadine MaleateNot AvailableNot Available
AzatadinumLatinINN
Salts
Name/CAS Structure Properties
Azatadine Maleate
Thumb Not applicable DBSALT000973
Brand names
NameCompany
IdumedNIHFI
OptimineSchering-Plough
ZadineFulford
Brand mixtures
Brand NameIngredients
CedrinAzatadine and Pseudoephedrine
Trinalin RepetabsAzatadine Maleate + Pseudoephedrine Sulfate
Categories
CAS number3964-81-6
WeightAverage: 290.4021
Monoisotopic: 290.178298714
Chemical FormulaC20H22N2
InChI KeySEBMTIQKRHYNIT-UHFFFAOYSA-N
InChI
InChI=1S/C20H22N2/c1-22-13-10-16(11-14-22)19-18-7-3-2-5-15(18)8-9-17-6-4-12-21-20(17)19/h2-7,12H,8-11,13-14H2,1H3
IUPAC Name
2-(1-methylpiperidin-4-ylidene)-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaene
SMILES
CN1CCC(CC1)=C1C2=CC=CC=C2CCC2=C1N=CC=C2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzocycloheptapyridines
SubclassNot Available
Direct parentBenzocycloheptapyridines
Alternative parentsBenzene and Substituted Derivatives; Pyridines and Derivatives; Piperidines; Tertiary Amines; Polyamines
Substituentspiperidine; pyridine; benzene; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzocycloheptapyridines. These are aromatic compounds containing a benzene ring and a pyridine ring fused to a seven membered carbocycle.
Pharmacology
IndicationFor the relief of the symptoms of upper respiratory mucosal congestion in perennial and allergic rhinitis, and for the relief of nasal congestion and eustachian t.b. congestion.
PharmacodynamicsAzatadine is an antihistamine, related to cyproheptadine, with anti-serotonin, anticholinergic (drying), and sedative effects. Azatadine is in the same class of drugs as chlorpromazine (Thorazine) and trifluoperazine (Stelazine); however, unlike the other drugs in this class, azatadine is not used clinically as an anti-psychotic. Antihistamines antagonize the vasodilator effect of endogenously released histamine, especially in small vessels, and mitigate the effect of histamine which results in increased capillary permeability and edema formation. As consequences of these actions, antihistamines antagonize the physiological manifestations of histamine release in the nose following antigen-antibody interaction, such as congestion related to vascular engorgement, mucosal edema, and profuse, watery secretion, and irritation and sneezing resulting from histamine action on afferent nerve terminals.
Mechanism of actionAntihistamines such as azatadine appear to compete with histamine for histamine H1- receptor sites on effector cells. The antihistamines antagonize those pharmacological effects of histamine which are mediated through activation of H1- receptor sites and thereby reduce the intensity of allergic reactions and tissue injury response involving histamine release.
AbsorptionWell absorbed after oral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityThe oral LD50 in mature rats and mice was greater than 1700 mg/kg and 600 mg/kg, respectively. Symptoms of overdose include clumsiness or unsteadiness, seizures, severe drowsiness, flushing or redness of face, hallucinations, muscle spasms (especially of neck and back), restlessness, shortness of breath, shuffling walk, tic-like (jerky) movements of head and face, trembling and shaking of hands, and insomnia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9973
Blood Brain Barrier + 0.9826
Caco-2 permeable + 0.7341
P-glycoprotein substrate Substrate 0.8357
P-glycoprotein inhibitor I Inhibitor 0.9232
P-glycoprotein inhibitor II Inhibitor 0.545
Renal organic cation transporter Inhibitor 0.8115
CYP450 2C9 substrate Non-substrate 0.8064
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.5716
CYP450 1A2 substrate Non-inhibitor 0.5801
CYP450 2C9 substrate Non-inhibitor 0.791
CYP450 2D6 substrate Inhibitor 0.6078
CYP450 2C19 substrate Non-inhibitor 0.8348
CYP450 3A4 substrate Non-inhibitor 0.835
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6425
Ames test Non AMES toxic 0.7616
Carcinogenicity Non-carcinogens 0.9692
Biodegradation Not ready biodegradable 0.9819
Rat acute toxicity 2.9760 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.804
hERG inhibition (predictor II) Inhibitor 0.6909
Pharmacoeconomics
Manufacturers
  • Schering corp sub schering plough corp
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point152-154REM p. 1131 Villani, F.J.; U.S. Patents 3,326,924; January 20, 1967; 3,357,986; December 12, 1967; and 3,419,565; December 31,1968; all assigned to Schering Corp.
water solubilityVery solubleNot Available
logP3.59BIOBYTE (1995)
Predicted Properties
PropertyValueSource
water solubility1.13e-01 g/lALOGPS
logP3.67ALOGPS
logP3.75ChemAxon
logS-3.4ALOGPS
pKa (strongest basic)7.91ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area16.13ChemAxon
rotatable bond count0ChemAxon
refractivity101.53ChemAxon
polarizability34.01ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Raymond E. Dagger, Linda A. Motyka, “Process for preparing intermediates for azatidine.” U.S. Patent US4954632, issued September 04, 1990.

US4954632
General Reference
  1. Zhang D, Hansen EB Jr, Deck J, Heinze TM, Sutherland JB, Cerniglia CE: Fungal biotransformation of the antihistamine azatadine by Cunninghamella elegans. Appl Environ Microbiol. 1996 Sep;62(9):3477-9. Pubmed
  2. Katelaris C: Comparative effects of loratadine and azatadine in the treatment of seasonal allergic rhinitis. Asian Pac J Allergy Immunol. 1990 Dec;8(2):103-7. Pubmed
  3. Small P, Barrett D, Biskin N: Effects of azatadine, terfenadine, and astemizole on allergen-induced nasal provocation. Ann Allergy. 1990 Feb;64(2 Pt 1):129-31. Pubmed
External Links
ResourceLink
KEGG CompoundC07774
PubChem Compound19861
PubChem Substance46507958
ChemSpider18709
BindingDB22868
ChEBI2946
ChEMBL
Therapeutic Targets DatabaseDAP001079
PharmGKBPA164747157
Drug Product Database355666
RxListhttp://www.rxlist.com/cgi/generic3/azatpseud.htm
Drugs.comhttp://www.drugs.com/mtm/azatadine.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tri1460.shtml
WikipediaAzatadine
ATC CodesR06AX09
AHFS Codes
  • 04:04.92
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
DonepezilPossible antagonism of action
GalantaminePossible antagonism of action
RivastigminePossible antagonism of action
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

Targets

1. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

  1. Singh N, Puri SK: Causal prophylactic activity of antihistaminic agents against Plasmodium yoelii nigeriensis infection in Swiss mice. Acta Trop. 1998 Jun;69(3):255-60. Pubmed
  2. Mann KV, Crowe JP, Tietze KJ: Nonsedating histamine H1-receptor antagonists. Clin Pharm. 1989 May;8(5):331-44. Pubmed
  3. Clissold SP, Sorkin EM, Goa KL: Loratadine. A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs. 1989 Jan;37(1):42-57. Pubmed
  4. Haria M, Fitton A, Peters DH: Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders. Drugs. 1994 Oct;48(4):617-37. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on January 08, 2014 10:20